The Global Road Safety Facility (GRSF) has developed this evidence-based guide on “What Works and What Does Not Work” in road safety in response to the critical need for effective evidence-based solutions. This guide has been prepared to help readers understand that not all road safety interventions are equally effective and that what appear to be “common-sense” approaches to selecting road safety interventions will often not be the best. Although some provide benefits, others have very limited or even negative impacts, despite being commonly—and mistakenly—recommended or accepted. The guide offers a range of recommendations with a focus on interventions in LMICs, although the information may also be of relevance to all countries. The contents will be valuable to those working on road safety at policy or practitioner levels, including World Bank technical team leaders and others who seek to establish, expand, or improve road safety programs in LMICs. The guide sets knowledge on evidence-based interventions within a “Safe System” context, providing advice on each of the Safe System pillars (road safety management, safe roads, safe speeds, safe vehicles, safe road users, and post-crash care) while recognizing that evidence-based solutions must be drawn from across pillars to produce effective road safety outcomes. At the core of this document is a summary table with an overview of beneficial and non-beneficial interventions based on sound scientific evidence. This is followed by more detailed information including case studies and references to the evidence base to support the summary.